FDA approves brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma
On July 24, 2020, the Food and Drug Administration granted accelerated approval to brexucabtagene autoleucel (TECARTUS, Kite, a Gilead Company), a CD19-directed genetically modified autologous T cell immunotherapy, for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL).
Approval was based on ZUMA-2 (NCT02601313), an open-label, multicenter, single-arm trial of 74 patients with relapsed or refractory MCL who had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody, and a Bruton tyrosine kinase inhibitor. Patients received a single infusion of brexucabtagene autoleucel following completion of lymphodepleting chemotherapy. The primary efficacy outcome measure was objective response rate (ORR) per Lugano [2014] criteria as assessed by an independent review committee.
Approval was based on ZUMA-2 (NCT02601313), an open-label, multicenter, single-arm trial of 74 patients with relapsed or refractory MCL who had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody, and a Bruton tyrosine kinase inhibitor. Patients received a single infusion of brexucabtagene autoleucel following completion of lymphodepleting chemotherapy. The primary efficacy outcome measure was objective response rate (ORR) per Lugano [2014] criteria as assessed by an independent review committee.
Of the 60 patients evaluable for efficacy based on a minimum duration of follow-up for response of six months, the ORR was 87% (95% CI: 75, 94), with a complete remission (CR) rate of 62% (95% CI: 48, 74). The estimated median duration of response was not reached (range of 0+ to 29.2+ months) after a median follow-up time for duration of response of 8.6 months. Of all 74 leukapheresed patients, the ORR as assessed by independent review committee (IRC) was 80% (95% CI: 69, 88) with a CR rate of 55% (95% CI: 43, 67).
The most common (≥10%) Grade 3 or higher reactions were anemia, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, pyrexia, hyponatremia, hypertension, infection – pathogen unspecified, pneumonia, hypocalcemia, and lymphopenia. FDA approved brexucabtagene autoleucel with a Risk Evaluation and Mitigation Strategy because of the risk of cytokine release syndrome (CRS) and neurologic toxicities.
The recommended dose of brexucabtagene autoleucel is a single intravenous infusion of 2 x 106 CAR-positive viable T cells per kg body weight (maximum 2 x 108 CAR-positive viable T cells), preceded by fludarabine and cyclophosphamide lymphodepleting chemotherapy.
This indication is approved under accelerated approval based on overall response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
FDA granted orphan drug designation, breakthrough therapy designation, and priority review to brexucabtagene autoleucel for this indication. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
FDA granted orphan drug designation, breakthrough therapy designation, and priority review to brexucabtagene autoleucel for this indication. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.
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